The long-range objective of this work is to determine the suitability of perfluorochemical emulsions as cardiac perfusates for investigative and clinical purposes. We have previously shown that the hemodynamic, mechanical, and energetic functions of isolated working rat hearts are more stable over a prolonged time period when the hearts are perfused with a perfluorochemical emulsion (Fluosol-43) than when they are perfused with crystalloid Krebs-Henseleit bicarbonate buffer. We now propose experiments to develop and characterize isolated working whole heart preparations from large animals (rabbits, lambs, pigs) using Fluosol-43 as perfusate. Hemodynamic and energetic function of the Fluosol-perfused hearts will be compared with that of hearts perfused with an erythrocyte-albumin-Krebs-Henseleit solution. Biochemical characterization of the rat heart and large heart preparations will include analysis of substrate utilization (glucose, lactate, oleate, acetate) and study of subcellular activities (mitochondrial respiration, myofibrillar ATPase, sarcoplasmic reticulum Ca++ uptake, sarcolemma slow inward calcium channel transport, K+ loss) during Fluosol perfusion. Rat heart perfusions performed with Krebs-Henseleit or with a colloidal control solution will help establish the mechanism of Fluosol's preservative effect on the isolated heart (increased oxygen delivery? increased oncotic pressure?). In later experiments we will study the function of Fluosol-43-perfused isolated working hearts under ischemic or hypoxic conditions. The development of isolated working heart preparations from rabbits, lambs, and pigs will permit the study of hemodynamics, physiology, and metabolism of those hearts under controlled biochemical and mechanical conditions. These preparations will have wide application, particularly in studies of fetal and newborn heart development and in experiments in which animal hearts that are anatomically and functionally similar to human hearts are needed. Our experiments will also help establish the subcellular mechanism(s) that contribute to the improved function of isolated hearts perfused with perfluorochemical emulsion and the mechanism(s) of the putative beneficial effect of perfluorochemical emulsion on ischemic hearts.